The present invention generally relates to the use of radiation therapy to treat a condition such as restenosis and more particularly pertains to the use of an implantable device to deliver a dose of radiation.
A variety of conditions have been found to be treatable by the local irradiation of tissue. In order to appropriately limit the amount of tissue that is irradiated, it is sometimes necessary to implant a small source of radiation and in order to expose the tissue to a sufficient dosage of radiation, it has been found advantageous to implant such device for an extended period of time.
Percutaneous transluminal coronary angioplasty (PTCA) is an established treatment for coronary artery disease. The procedure involves inserting a balloon catheter through the vasculature to a position where atherosclerotic plaque has collected on the vessel wall. The plaque is compressed against the vessel wall by inflating the balloon located at the distal end of the catheter in order to increase the diameter of the vessel and thereby reduce the restriction to blood flow. After sufficient expansion has been achieved, the balloon is deflated and removed, and the area of disruption begins to heal.
While this procedure is very widely used, one problem associated with PTCA is a condition known as restenosis. Restenosis is the development of further blockage in the intravascular structure, following an otherwise successful angioplasty procedure and is believed to be an exaggerated form of the normal healing process of the stretched tissue. Restenosis is thought to be caused by fibrointimal proliferation of the stretched wall in which the injured cells lining the vascular structure multiply and form fibrous tissue. Such growth at the vascular wall is an almost malignant phenomenon in which normal cells multiply at a high rate, thereby creating a new obstruction to flow through the vascular structure. It occurs in the range of approximately 15-50 percent of the cases and typically within the first six months following PTCA. Stents have been implanted in expanded vessels in an effort to maintain patency but do not appear to have much of an effect on the restenosis rate. In the event a stent has been implanted, the growth tends to occur around its ends and through any openings in its walls.
The localized irradiation of the vessel from within the vessel has been found to be effective in reducing the incidence of restenosis. Such radiation has to date been delivered via a number of different vehicles including by guide wire, balloon, temporarily implantable wire or permanently implantable stent. The delivery device is either partially or wholly formed of radioactive material or alternatively, is coated with a radioactive substance. Material giving off high levels of radiation may be briefly introduced into the body and then removed. Alternatively, material giving off a relatively lower level of radiation and with an appropriately short half-life may be introduced temporarily or alternatively left in place.
A number of shortcomings or disadvantages are associated with the prior art devices and techniques. With respect to temporarily implanted devices, implantation time is limited and therefore the radiation dose must necessarily be very high. At such high dosage rates, local radiation burns may be caused on one side of the vessel while the opposite side may receive a suboptimum dose. Moreover, due to the tendency of restenosis to occur throughout a six month period, repeated irradiation procedures would be necessary in order to adequately address the vagaries of onset.
In the case of permanently implanted devices, a compromise must be made between the shelf life of the device and its in vivo efficacious lifetime. If materials with short half-lives are used in order to reduce the long term exposure of the patient to radiation, then the shelf life of the device must necessarily be short and therefore unacceptable. If on the other hand, an isotope is used which will result in a substantial shelf life, i.e., an isotope having a long half-life, then the exposure of the patient to radiation will be long term and may be excessive. Moreover, in view of the fact that the development of restenosis typically occurs within the first six months, it has been recognized that it is desirable to limit irradiation to such time frame. Of course, attempting to substantially restrict the release of radiation from a permanently implantable device to such a limited period of time imposes further constraints on the shelf life of the device.
Another disadvantage inherent in the heretofore known delivery devices is the necessity to adequately protect all who handle the device, including the manufacturing, stocking, and shipping personnel, catheter laboratory personnel, and physicians from exposure to unreasonable radiation dosages. This requires the use of large and cumbersome containers that further complicate handling and disposal concerns. Some of the radioisotopes being considered in the industry require ion implantation into the device or transmutation of the metal in the device. The complexity of such processes greatly increases the cost of the devices.
A new approach is necessary that would overcome the shortcomings of the prior art. It would be desirable to provide a system by which a very predictable dosage of radiation can be delivered via a permanently implantable device. Moreover, it would be most desirable for such device to be producible at minimal cost, to have a substantial shelf life and present a minimal risk of exposure to radiation.